Abstract
BackgroundBacterial gastroenteritis causes morbidity and mortality in humans worldwide. Murine Citrobacter rodentium infection is a model for gastroenteritis caused by the human pathogens enteropathogenic Escherichia coli and enterohaemorrhagic E. coli. Mucin glycoproteins are the main component of the first barrier that bacteria encounter in the intestinal tract.Methodology/Principal FindingsUsing Immunohistochemistry, we investigated intestinal expression of mucins (Alcian blue/PAS, Muc1, Muc2, Muc4, Muc5AC, Muc13 and Muc3/17) in healthy and C. rodentium infected mice. The majority of the C. rodentium infected mice developed systemic infection and colitis in the mid and distal colon by day 12. C. rodentium bound to the major secreted mucin, Muc2, in vitro, and high numbers of bacteria were found in secreted MUC2 in infected animals in vivo, indicating that mucins may limit bacterial access to the epithelial surface. In the small intestine, caecum and proximal colon, the mucin expression was similar in infected and non-infected animals. In the distal colonic epithelium, all secreted and cell surface mucins decreased with the exception of the Muc1 cell surface mucin which increased after infection (p<0.05). Similarly, during human infection Salmonella St Paul, Campylobacter jejuni and Clostridium difficile induced MUC1 in the colon.ConclusionMajor changes in both the cell-surface and secreted mucins occur in response to intestinal infection.
Highlights
Bacteria such as enteropathogenic Escherichia coli (EPEC), enterohaemorrhagic E. coli (EHEC), Salmonella enteritidis and Clostridium difficile are major causes of infectious diarrhea in humans worldwide
Bacteria harvested from plate cultures were suspended in warmed Lauria-Bertani broth. 8 mice were orally inoculated with 107 colony forming units (CFU) and sacrificed after 12 days by cervical dislocation
C. rodentium infection and associated pathology is greatest in the large intestine
Summary
Bacteria such as enteropathogenic Escherichia coli (EPEC), enterohaemorrhagic E. coli (EHEC), Salmonella enteritidis and Clostridium difficile are major causes of infectious diarrhea in humans worldwide. C. rodentium is a natural mouse pathogen that is related to, and uses the same molecular mechanisms of type III secretion and attaching and effacing lesions as human EPEC and EHEC, to colonise the epithelial cells of the gut, providing a good in vivo model for gastroenteritis due to these bacteria [3,4]. The gastrointestinal tract is lined by a continuously secreted mucus layer formed by high molecular mass oligomeric mucin glycoproteins. Cell-surface mucins are likely to play an important role in mucosal defense since they may provide both a barrier and reporting function, and we have demonstrated increased pathology following gastrointestinal infection in mice lacking the Muc cell surface mucin [5,6]. Mucin glycoproteins are the main component of the first barrier that bacteria encounter in the intestinal tract
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